The therapeutic effectiveness of a drug depends on its bioavailability. More specifically, the term “bioavailability” refers to a measure of the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. See Food and Drug Administration regulation C.F.R. 21 §320.1(a). In particular, the bioavailability of a drug once it is administered correlates to the drug's solubility. See U.S. Dept. of Health and Human Services, FDA, Center for Drug Evaluation and Research “Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System,” (August 2000). As of 2008, approximately 30% of the drugs that appeared on the World Health Organization (WHO) Essential Drug List were poorly water-soluble, based on the Food and Drug Administration (FDA)'s Biopharmaceutics Classification System (BCS) Tam J M, et al. J. Pharm. Sci. 97(11):4915-33 (2008). The poor dissolution of these drugs often results in the drugs having low and highly variable bioavailabilities. A major obstacle of successfully commercializing poorly water-soluble drugs is the difficulty of enhancing their dissolution rates and extents of dissolution. Therefore, a need exists to develop pharmaceutical formulations that increase the solubilities of poorly water-soluble drugs.
The preparation of a pharmaceutical formulation that comprises a poorly water-soluble drug generally requires a step that dissolves the poorly water-soluble drug in an organic solvent in combination with a lipid substance. In addition, such preparations frequently require that solubilizing aids be used to enhance the dissolution of poorly water-soluble drugs. However, solubilizing aids typically need to be dissolved in water or water-miscible solvents rather than organic solvents. Predictably, the step of mixing the organic solution that contains the drug and the lipid with the aqueous solution that contains the solubilizing aid creates the expectation that the solutes will precipitate out of solution. The consequence of a precipitation event is that a powder formulation prepared from the solution would no longer be homogenous, thereby complicating the performance or processing of the formulation. This invention, however, optimizes a composition of organic and aqueous solvents, surfactant, a poorly water-soluble drug substance, and a solubilizing aid to obtain a clear, non-precipitating, homogenous solution that can be easily converted into a free flowing powder formulation.